EDITORIAL
It is my pleasure to introduce to you the eleventh issue of Phenotype magazine! As always, this
issue includes contributions from PIs, post-docs and students from across the University.
A highlight of this issue is an introduction by Dr Phil Biggin, RCUK Fellow in the
Department of Biochemistry, to his research using computational approaches to examine
ligand binding to receptor proteins. Also featured is an interview with Prof Adrian Hill,
director of the Jenner Institute, in which he shares the highlights (and travels) of his career in
tropical medicine thus far.
This issue has a strong focus on advances in genetics and how this affects us all. William
Brandler starts the discussion by introducing the “500 Genome Project” of The Wellcome
Trust Centre for Human Genetics and how whole genome sequencing can be used to identify
the genetic basis of diseases. Annabel Morley looks more closely at what can be done once
genetic diseases are identified, namely gene therapy. She explores how close this treatment is to
becoming a clinical reality, describing recent advances in how gene therapy might be delivered. Finally, Mark Pavlyukovskyy moves the
discussion to genetic modifications that can already be accomplished and how we as a society view them, summarising the current state
of genetically modified food in the EU and the challenges for the future.
Moving away from genetics, Richard Wheeler gives us an insight into how economists view academic science, describing the theory
of gift economics. We also showcase a blogger from the Oxbridge Biotechnology Roundtable, Sonya Hanson, who wonders about the
future of biotech investment in a post-recession world.
Finally, in our Science and Society section, Clara Ferreira introduces us to the Athena SWAN award, which promotes gender equality
in the science, engineering and technology sector, and Blanka Sengerová shares her experiences of volunteering at Science Oxford.
The image gracing this issue’s cover was submitted by Dr Elizabeth Hartfield and was the winner of last issue’s SNAPSHOT prize.
Learn more about her work using skin cells from Parkinson’s patients to first create stem cells, then differentiated neurons, on page 31.
There is another chance to win £50 from Oxford University Press this issue and we look forward to your research-inspired images.
Congratulations to our regular contributor, Penny Sarchet, for her recent win of the Wellcome Trust science writing prize! Read her
past contributions, Ghost Forest in Issue 8 and Bugs that eat Oil in Issue 9. If you are considering a career in science journalism after the
DPhil, or you just love to write, Phenotype is the place to hone your talents while at Oxford. If you would like to get involved in any
aspect of the magazine, from writing to editing to design, please contact us at oubs@bioch.ox.ac.uk.
This issue is a result of the hard work and dedication of our team of students and post-docs. Thank you for making my job an easy one,
and producing what I’m sure everyone can agree is a superb issue!
Jennifer de Beyer
Department of Biochemistry

n Monday 13 February, OUBS is hosting
Prof Peter Leadlay from the Department
of Biochemistry, University of Cambridge. He is
currently researching the molecular genetics and
chemistry of polyketide antibiotic biosynthesis.
Polyketides are a large class of microbial metabolites
produced by soil-based bacteria such as Streptomyces
spp.. They comprise useful antibiotics such as
erythromycin A, anticancer drugs such as doxorubicin
and antiparasitics such as avermectin. Polyketide
production is one of the major branches of the
pharmaceutical industry and such compounds
comprise 20% of the top-selling drugs. Work by
Leadlay’s group revolves around the production
of new polyketides with improved or novel
pharmacological properties, a process favoured by the
modular nature of polyketide synthases.
Polyketides are classified both on the basis of their
structure and their mode of biosynthesis. The most
interesting polyketides for genetic engineering are
the reduced polyketides, in which the first linear
chain is constrained by macrocyclisation into a
biologically active conformation. This promotes
targeted and precise interaction with their protein
partners. Reduced polyketides are further subdivided
into macrocycles and polyethers. Macrocycles contain
a lactone or lactam ring, while polyethers bear a
carboxylate group and two to five ether oxygen atoms.
Genes coding for polyketide synthases have a
modular organisation. Polyketides are built on a
molecular assembly line with an enzymatic domain
for each biosynthetic step. The modules are organised
into multimodular subunits, with a typical subunit
containing two or three modules. Many polyketide
synthases receive their substrates from enzymes
that catalyse prior steps in the synthesis and not by
diffusive loading, implying that the enzymes have
not been under an evolutionary pressure to develop
strict substrate specificities. Indeed, genes coding for
individual domains or entire modules can be replaced
or substituted to generate chimeric genes coding
for engineered polyketide synthases. These in turn
generate polyketides with altered stereochemistry or
functionality.
However, there are currently caveats that hamper
the creation of novel polyketides. Many domains
have degrees of substrate specificity that prove
difficult to change, and controlling stereochemistry
is complicated by a complex interplay between
ketosynthase and ketoreductase domains. The spatial
relationship between domains within the modules
that enable them to cooperate sequentially is not well
understood, but must be conserved in engineered

enzymes. The structure of polyketide synthases is not
well characterised, making it hard to arrange correctly
positioned subunits for synthesis solely of targeted
products. Lastly, engineering polyketide synthase
systems is tedious due to the large size of polyketide
gene clusters.

by Maria
Mogni

Nonetheless, Leadlay’s group has contributed to the
development of several new polyketides, as well as
to the understanding of the pathways behind their
synthesis. For example, an analysis was performed
of the role in stereochemistry of certain amino acids
in the active site of a ketoreductase. It was found
that additional factors such as tethering of the
substrate to an acyl-carrier protein might play a role
in ketoreductase stereospecificity (1). Furthermore, a
study was conducted in order to isolate and identify
intermediate species which are usually covalently
attached to their biosynthetic enzymes (2). This led
to the development of a chemical strategy based
on a competition effect between carba(dethia)
substrates and acyl carrier proteins, the former
causing the premature release of intermediates from
polyketide synthases. The group has also contributed
to the identification of new enzymes involved in
the biosynthesis of specific polyketides, such as an
enzyme acting on chorismate for the synthesis of the
important immunosuppressant drug rapamycin (3).

Resveratrol, a
phytoalexin found
in grapes and other
food products, was
shown to have cancer
chemopreventive
activity.
This snapshot of Professor Peter Leadlay’s research
underlines the important role of polyketides
in biomedical research, whereby combinatorial
biosynthesis is key to the generation of novel
compounds.
References:
1. Kwan D, et al. (2011) Insights into the
stereospecificity of ketoreduction in a modular
polyketide synthase. Org Biomol Chem 9(7):2053–2056.
2. Tosin M, et al. (2011) In vivo trapping of polyketide
intermediates from an assembly line synthase using
malonyl carba(dethia)-N-acetyl cysteamines. Chem
Commun 47(12):3460–3462.
3. Andexer J, et al. (2011) Biosynthesis of the
immunosuppressants FK506, FK520, and rapamycin
involves a previously un-described family of enzymes
acting on chorismate. PNAS 108(12):4776–4781.

Hilary 2012 | Phenotype | 5

A selection of recent life sciences research from the University of Oxford

Glutamine analogs promote
cytoophidium assembly in human and
Drosophila cells
Cellular compartmentalisation of CTP synthase
enzyme in structures termed cytoophidia occurs
in bacteria, yeast and fruit flies. More recently,
such filamentous structures have been identified in
humans. Cytoophidia in human cells were found
by immunostaining HeLa P4 cells with antibodies
against CTP synthase, revealing filamentous
structures.
The conservation from prokaryotes to eukaryotes
indicates that cytoophidia have a crucial function
within cells. CTP synthase is an essential metabolic
enzyme involved in pyrimidine biosynthesis
from both de novo and uridine interconversion
pathways. The rate-limiting reaction catalysed by
CTP synthase is the hydrolysis of glutamine in a
glutamine amidotransferase domain to produce
ammonia. Glutamine analogues such as 6-diazo-5oxoL-norleucine (DON) inhibit enzyme activity by
acting as a receptor antagonist irreversibly binding
to the enzyme’s catalytic centre. In the bacterium
Caulobacter crescentus, DON abolishes cytoophidium
formation. Surprisingly, in human cells DON
treatment increases the occurrence of cytoophidia.
This difference is puzzling, but could be explained
by the differences between prokaryotic and
eukaryotic cells, or the exposure time of DON in
the studies – bacterial treatment was shorter than its
human and fly counterparts. It is hypothesised that
the induction of cytoophidium formation by DON
might be a compensation mechanism responding
to its inhibition of CTP synthase activity. Another
glutamine analogue, azaserine, had comparable
effects to DON.
Clonal analysis by CTP synthase RNA interference
(RNAi) showed that CTP synthase expression levels
are crucial for cytoophidia formation. Nevertheless,
DON promotes cytoophidium assembly when CTP
synthase levels are low. Experiments showed DONinduced cytoophidium formation in flies occurs in
a wide range of tissues, including larval and adult
testes, and trachea and larval epithelial stem cells.
Increased CTP synthase activity is observed in
many cancers, hence inhibitory DON has been
trialled as an anti-tumour agent. Further studies are
also needed to ascertain whether the abundance of
cytoophidia is a potential cancer biomarker.
Cytoophidia occurrence in human cells increases
upon treatment with DON, responding in a

Vitamin D–gene interactions in
multiple sclerosis
Gene-environment interactions can be crucial in
disease risk. Vitamin D (VitD) deficiency has been
linked to multiple sclerosis (MS), but the molecular
mechanisms are unclear.
VitD is a group of fat-soluble steroids that
function as prohormones in humans; it is primarily
synthesised by the body as vitamin D3 and then
enzymatically converted to its active form 1,25dihydroxyvitamin D (known as calcitrol). VitD
mediates its biological effects by binding to the
vitamin D receptor (VDR), which is principally
located in the nuclei of target cells. After binding
to the retinoid-X receptor, this complex binds to
specific genome sequences called VitD response
elements (VDREs) in the nucleus where it can
regulate transcription of multiple hormone-sensitive
genes.
The incidence of MS rises with increased latitude
and decreasing levels of UVB radiation, which
correlates to VitD levels. To ascertain the molecular
basis for this association, Berlanga-Taylor et al.
searched for VDREs in regulatory elements within
the major histocompatibility (MHC) class II region.
In silico analysis showed that a VDRE existed
close to the promoter region of HLA-DRB1, the
main risk variant for MS. Recruitment of VDR
to this region was also indicated. Furthermore,
increased expression of HLA-DRB1*15 occurred
upon VitD stimulation. These findings provide
strong molecular evidence for an environmental
factor directly interacting with the highest MS risk
variant. A genome-wide map of VDR binding,
using chromatin immunoprecipitation and DNA
sequencing, identified 2776 VDR binding locations.
Many other genes associated to MS were discovered
to be regulated by VitD, including IRF8 and
CD226.
There is considerable evidence in support of VitD
deficiency underlying risk for several diseases,
including MS, rheumatoid arthritis and type I
diabetes. With the molecular mechanism for action
of VitD in MS now revealed, the evidence could
lead to disease prevention studies.

The dynamics of receptors
H

by Dr
Phil Biggin

ow do receptor proteins transmit a signal? Knowledge of this process, which usually
involves a change in conformation, is useful not only for our basic understanding of how
these proteins work, but also for improving our prospects for drug design. Indeed there is an
increasing feeling that modulation of receptors rather than outright block will become the way
forward for novel drugs. My group uses computational methods to explore the dynamics of
receptors with a long-term view to developing alternative strategies for drug design.

Receptors are dynamic
Receptors are a class of macromolecules that
specifically and directly convey a signal, typically in
the form of a smaller molecule, between or within
cells. A receptor must not only recognise the particular
molecule that activates it but also, when recognition
occurs, alter cell function. This invariably involves
the receptor undergoing a conformational change
such that other proteins can now interact with the
receptor, leading to a cascade of signalling events that
might, for example, lead to a change in transcriptional
activity. Alternatively, the conformational change
can lead to the opening of ion-channels to allow the
depolarisation of the cell. Examples of the latter are
the ionotropic glutamate receptors (iGluRs).
The iGluRs are responsible for the majority of fast
neurotransmission in the brain and central nervous
system and therefore are involved in memory and
learning (1). Because of their centrality to brain
function, it is perhaps unsurprising to find these
receptors implicated in many neurological diseases
including Parkinson’s, Huntington’s and epilepsy.
The receptors are ligand-gated ion channels situated
in synaptic membranes. Glutamate, the agonist,
is released from the pre-synaptic neuron, diffuses
across the synaptic cleft and binds to iGluRs.
The binding event leads to ion channel opening,
which then allows sodium ions to pass into the cell.
This in turn depolarises the membrane, initiating
an action potential which continues down the
length of the neuron. After prolonged exposure to
glutamate, the receptors desensitise, undergoing
further conformational changes to close even though
glutamate is still bound.
Determining iGLuR structure
The iGluR family, which can be divided into three
sub-families based on their response to different
pharmacologically relevant compounds, are large
tetrameric assemblies. Each subunit has an unusual
modular architecture (Figure 1A). In particular, the
ligand-binding domain (LBD) appears to have a
complete potassium-channel fold inserted into its
polypeptide sequence. Both the amino-terminal
domain (ATD) and the LBD have an overall structure
similar to periplasmic-binding proteins and are
essentially the shape of a Pac-Man or a clam-shell.
This provides the first clue as to how the receptor is

10 | Oxford University Biochemical Society

able to couple the binding of a neurotransmitter into
mechanical work that allows the transmembrane
(TM) pore to open.
The modular nature of the receptor allowed a
‘divide and conquer’ approach to be taken in terms
of obtaining structural data. Arguably the most
significant step was to make a protein construct that
corresponded to the LBD alone, maintained the
binding properties of the full-length receptor, and
could be readily crystallised (2). More recently a fulllength crystal structure of a tetramer has been solved
(3) which supports not only the crystal structures of
the isolated domains, but also the expectation that the
TM region would be similar to potassium channels
(Figure 1B). The full length structure also revealed
that the TM region exhibits true four-fold symmetry
which appears to break down as the protein exits
the membrane, such that the extracellular domains
are best thought of as a dimer of dimers. Finally, the
ATD appears to exhibit domain swapping, although
whether this is a genuine feature in vivo or an artefact
of the crystallization process remains to be seen.
The combination of structural data with years of
mutagenesis and pharmacological studies has led to
an overall cartoon of channel function (Figure 1C).
Glutamate binding allows the LBD to pull open
the TM pore. After a period of time, the receptor
undergoes desensitisation and that is thought to
reflect a change in the dimer interface allowing
the pore to close even though glutamate remains
bound. Despite a huge amount of experimental data,
the precise nature of the conformational changes
remains little more informed than our low-resolution
cartoons. In part, this is because there are few,
if any, experimental tools that can address these
dynamic questions at atomic resolution. This is where
computational techniques, and in particular molecular
dynamics, can be used to gain further mechanistic
insight.
Molecular dynamics
Molecular dynamics (MD) computes the movement
of atoms as a function of time. The potential energy of
the configuration of the system, given by the atomic
coordinates, is described by a force-field. The forces
acting on the atoms are computed using Newton’s
equations and this is used to drive the evolution of the

system forwards in time. The end result is a trajectory,
or ‘movie’, comprised of several snapshots at each time
interval. This alone can provide enormous insight into
the behaviour of proteins in general.

-

+

O

O

We and subsequently others have shown that the
overall flexibility of the LBD is also directly related
to the type of agonist bound (7, 8). Full agonists
appear to induce a more ‘rigid’ LBD, which might
be important for how efficiently the binding
signal is transmitted to the TM domain. MD also
predicted that the LBD could readily open to a
more open structure than had been observed by
X-ray crystallography, supported by small-angle
X-ray scattering (SAXS) data (9). Detailed free
energy calculations suggested that 9-12 kcal/mol
becomes available upon binding glutamate to drive
the conformational change that is required to open

D1
O

The structures of the LBD revealed that agonists and
partial agonists bind to the middle of the clam-shell,
thus stabilising a closed-cleft conformation (middle
panel of Figure 1C). Partial agonists appear to stabilise
the clam-shell with a degree of domain closure
directly proportional to the efficacy of the agonist.
In other words, the more efficacious the agonist, the
‘more closed’ the clam-shell is (4, 5). Conceptually
this was attractive because one can imagine that a
full agonist would induce full domain closure which
in turn would pull on the pore-lining M3 helices to
a maximal opening. Partial agonists would do the
same but to a lesser extent. However, single channel
experiments reveal that partial agonists are capable
of opening up the channel to the same conductance
levels as full agonist, but also, and rather importantly,
that this occurs less frequently (6). Thus, partial
agonists are less efficient at inducing channel opening
and the static picture from the crystal structures is a
bit misleading.

ATD

NH 3

Beyond cartoons
So what can MD contribute to our understanding of
iGluR function? The first area where simulation has
been applied extensively is to understanding the role
that dynamics might have within the LBD.

B

O

However, molecular dynamics can provide much more
information than just the “wiggling and jiggling”,
as Richard Feynman might have put it. With recent
increases in computational power, we can also obtain
free energies of processes such as conformational
change and binding events. Quantities such as free
energy reflect an ensemble of states. According to
the ergodic hypothesis, the time average provided by
MD should be the same as the ensemble average. This
allows us to relate what we see for a single molecule
to an experiment that records an ensemble. The only
proviso is that we must have performed the dynamics
for a long enough time-period. This is sometimes
called the ‘sampling problem’ and is the main reason
why many of these calculations were hitherto
prohibitive.

A

D2
OUT
M1

M3 M4
M2

IN

C
D1

D1

D2

D2

OUT
M3
IN

M3

Resting

Open

Desensitized

Figure 1. (A) Schematic cartoon of the ionotropic glutamate receptor
subunit topology. The LBD comprises two discontinuous regions of
polypeptide chain that form two structural lobes or sub-domains (D1 and
D2). The LBD and ATD have similar overall folds. Note that the architecture
of the transmembrane region resembles that of an upside-down potassium
channel. (B) Cartoon of the X-ray structure of the full-length structure.
Chains are coloured green, blue, gold and red. The structure shows domainswapping in the ATD relative to the rest of the protein. (C) A schematic
cartoon of the major changes in conformation as we imagine them. Only
two subunits and the LBD and M3 from the TM domain are shown for
clarity. The receptor starts off in the resting state with the channel closed
(pinched off by the ends of the M3 helices). Upon ligand-binding, the D1
and D2 lobes move together allowing mechanical work to be done to pull
the M3 (and M1) helices to open the pore. After a period of time, despite
the continued presence of agonist (glutamate), the receptor closes into a
desensitised state, thought to be due to a rearrangement of the interface
between the D1 lobes of adjacent subunits.
the channel (10) and more recently, we have been
able to identify a single salt-bridge rearrangement
that appears to control whether the cleft will close or
remain open (11). Thus, we are beginning to put some
dynamic detail on critical motions of the LBD.
Unanswered Questions
The full-length structure solved in 2009 generated
more questions than answers. For example, the
cartoons for the mechanism of opening suggest that
closure of the LBD opens the channel by pulling on
the M1 and M3 helices. Yet initial MD simulations
reveal that this mechanism is not immediately
compatible with the solved structure. The full-length
crystal structure was solved with an antagonist bound

Hilary 2012 | Phenotype | 11

A

teepee formed by the M3 helices (Figure 2C). It is
clear that additional motions are required to allow the
M3 helices to move far enough apart to allow ions to
flow through. Thus the mechanism by which LBD
closure leads to channel opening remains far from
obvious and will keep us busy for some time yet.

Figure 2. (A) Overlay of
pore-lining TM helices from
the closed state of the KcsA
potassium channel (red)
with the pore-lining helices
from the glutamate receptor
structure (cyan). The similarity
supports the view that the
crystal structure is in the resting
(closed) state. (B) Overlay of
the M1-M3 of the glutamate B
receptor (cyan) with the KcsA
potassium channel in a partially
open (gold) and open (green)
state, illustrating the potential
direction the pore-lining helices
might be expected to travel in
to open the channel. (C) A view
from the synapse showing the
position of the pre-M1 cuff
(grey) which appears to hinder
the postulated opening motion
of the glutamate receptor. M3
(pore-lining) helices are shown C
in cyan, M1 helices are red and
M4 are shown in gold.

I thank Dr Ranjit Vijayan for some of the figures used
in this article and Dr Maria Musgaard for helpful
comments.
References:

CLASH!

in the ligand-binding clefts. This corresponds to a
resting, closed state. However, we do have crystal
structures of the isolated ligand-binding cores with
agonists bound, corresponding to the open state of
the channel, so by overlaying the D1 sub-domains we
can get an idea of the direction that the forces exerted
by the LBD should act in. Furthermore, because the
TM domain of iGluRs is evolutionarily related to
potassium channels, comparison to crystal structures
of the open-states of those channels can be used to
infer how the iGluRs might open (Figure 2A & B).
However, when this is examined with MD the M3
helices that line the pore hardly move at all, even
when artificially ‘pushed’ in the postulated directions
(Figure 2B & C). There are two reasons for this.
Firstly, the linker regions are quite long, unstructured
sections of protein which appear to dissipate the
mechanical work done by the LBD. Secondly, the
TM region is ‘locked’ by the presence of a so-called
‘pre-M1 cuff ’, which acts like a ring on the top of the

Dr Phil Biggin is the RCUK Fellow in Structural
Bioinformatics and Computational Biochemistry
in the Department of Biochemistry, University of
Oxford.

Hilary 2012 | Phenotype | 13

Six billion to one

ASS TO GAS

How whole genome sequencing can improve our health and
even help us find love

by William
Brandler

Our evolution has shaped us to choose partners based on subtle cues that reflect both their
genetic fitness and compatibility with us. As our understanding of human genetic variation
becomes more complete, we could skip this imperfect system and go straight to the source, our
genetic code. Internet dating websites could spring up where lonely hearts are matched up using
not only their personalities and interests, but also their genetic compatibility. Couples could be
paired to maximise the likelihood of their offspring having user-specified ‘desirable traits’, while
minimising the risk of genetic diseases – the end result being ‘designer babies’. Regardless of the
ethical and moral considerations, the pace of the genetic revolution is such that this could be a
reality in the next few years.

The Genetic Revolution
Before the sequencing of the human genome in
2001, next to nothing was known about the genetics
of common human traits. Moving forward just
10 years to June 2011, there were 1,449 published
mutations identified that influence variation in 237
human traits (1). Prior to 2001, the molecular basis
of approximately 100 rare, monogenic disorders was
known. This number has jumped 30-fold such that
we now know the genes behind almost half of the
7,000 known monogenic disorders (2).
These numbers have been increasing exponentially
as the cost of genome sequencing technologies has
nosedived (Figure 1). As Richard Resnick, CEO
of genetic software firm GenomeQuest puts it (3),
this drop in the cost of genome sequencing “is the
equivalent of filling up your car with gas in 1998,
waiting until 2011 and now you can drive to Jupiter
and back, twice.” It will not be long before this
analogy can be pushed beyond our solar system.
The human genome project was a monumental
international effort that cost upwards of £2 billion.
As of October 2011, the biotech firm Illumina was
offering whole-genome sequencing for as little as
£5,000 for people with a life-threatening genetic
disease and for around £7,500 for people with
cancers that require the sequencing of both tumour
and non-cancerous cells (4). Soon it will be affordable
for the NHS to routinely sequence the genomes of
patients. Jay Flatley, CEO of Illumina, believes that
all babies born a decade from now will have their
genetic code mapped at birth (5).
Personalised medicine
This freefall in cost is driving a revolution in
medical genetics that is catalysing a shift in the
understanding, prevention, and treatment of genetic
diseases. The information gathered from genome
sequencing is ushering in an era of personalised
medicine, where individuals are given treatments

14 | Oxford University Biochemical Society

tailored to their genetic makeup. This is because
some drugs are only effective if patients carry specific
mutations. For example, mutations in the epidermal
growth factor receptor gene, EGFR, are present in
around 15% of lung cancers (6). The anti-cancer drug
gefitinib is only effective in this 15% of patients (6,
7), but costs more than £15,000 for each course of
treatment. In 2005, France decided to pay for the
treatment of every citizen who would benefit from
targeted drugs like gefitinib (8) and screened 15,000
patients for mutations in the EGFR pathway, of
which 1,700 tested positive. These patients were
given a full course of treatment at a cost of around
£30 million (8). To give every patient an initial eight
week course of gefitinib to see if they would respond,
and then only continue treating those who did,
would have cost nearly triple this figure. There are 15
drugs like gefitinib that have already been approved
by the European Medicines Agency (8) and many
more will follow. Personalised medicine will make
medical practice more effective and efficient.
Whole genome sequencing for disease diagnosis
To effectively treat a disease, you first need to know
its cause. Clinical geneticists have therefore started
offering whole genome sequencing to individuals
with unexplained life-threatening genetic disorders.
For example, a team led by Dr David Dimmock at
the Medical College of Wisconsin in Milwaukee
sequenced the genome of an infant diagnosed with
acute liver failure and identified mutations that
affected both copies of a gene called TWINKLE (7).
Mutations in this gene have previously been shown
to cause progressive neurological and eye disorders,
with two cases also presenting with liver disease. In
this case, the child was not recommended for a liver
transplant and died six months later. As Dimmock
explains, “This was not a happy ending – but in a
sense it was” (4). A child was spared a gruelling,
costly and unnecessary treatment, the parents were
spared false hope, and a liver was saved for another
child who may have had greater need.

Following on from these initial results, larger scale
sequencing of human genomes has now begun.
In August 2011, The Wellcome Trust Centre
for Human Genetics in Oxford teamed up with
Illumina to sequence the genomes of 500 people
with various genetic diseases, ranging from cancer to
immunological disorders and rare inherited diseases
(9).
Knowing the cause does not guarantee a cure
Despite these technological advances, whole
genome sequencing provides a wealth of data that
is incredibly challenging to interpret and convey to
patients. It requires sifting through the six billion
letters that make up our genetic code, searching
for one, or a handful of, causative mutations. Even
if the gene responsible can be identified, it may
not be treatable. For example, Tay-Sachs disease
is a progressive neurological disorder caused by
mutations in the HEXA gene, for which there is no
cure. For many genetic disorders, short of using gene
therapy to replace the defective copy of the gene in
every cell in your body before it has an irreversible
effect, there will be no cure.
Furthermore, the results of genome sequencing may
throw up some unwelcome incidental findings. You
may not want to know your fate if it turns out you
carry mutations that cause an incurable Mendelian
disorder like Huntington’s or early onset familial
Alzheimer’s disease.
Genes are not our destiny
For more common, multigenic disorders like heart
disease, diabetes and cancer, the letters of your genes
do not spell out your destiny. If you know the risks,
you can make lifestyle changes to minimise them.
However, even the largest scale studies have yet to
do more than scratch at the surface of understanding
the genetic basis of common human traits. For
example, a study of human height in 180,000
individuals has found variants that account for only
10% of the observed phenotypic variation (10).
As we perform ever larger and more sophisticated
studies, we will begin to close the gap on this
‘missing heritability’ of genetic traits.
Companies like 23andme have sprung up in the last
few years offering to genotype specific regions of
the genome that are associated with known human
traits and diseases. As costs plummet, there is no
doubt that these companies will offer whole genome
sequencing. It is only a matter of time before internet
dating websites join them.

Figure 1. The cost per human genome has dropped significantly since the
completion of the human genome project (11). This has far outstripped
Moore´s law, which describes the doubling of computer power every two
years. Wetterstrand KA. DNA Sequencing costs: Data from the NHGRI
Large-Scale Genome Sequencing Program. Available at www.genome.gov/
sequencingcosts. Accessed January 2012.

William Brandler is a 3rd year DPhil student in Prof Anthony Monaco´s
laboratory at the Wellcome Trust Centre for Human Genetics, University
of Oxford.

Hilary 2012 | Phenotype | 15

Gift economics and science
by Richard
Wheeler

Y

ou will have heard of gifts and of economics, but probably not of gift economics. This
economic structure completely ignores bartering and money. Instead, you are expected to
give away your time, skills or belongings for free. In a gift economics world, instead of going to
work and earning money in return, you spend the day working for free and when you head home,
you stop at the supermarket and pick up a bag full of shopping without paying.

This economic system is the complete inverse of
capitalism and in today’s world, which is driven by
trade, seems very backwards. There are now very
few communities that base their everyday lives on
gift economies. Hundreds, if not thousands, of years
ago, the vast majority switched from giving gifts to
bartering and trade. Given this, you can be forgiven
if you have not heard of gift economics. However
you may be surprised that the research conducted
at Oxford University is actually part of one of the
biggest gift economies active in the world today.

Figure 2. Gift
economies.
Many of the most
recognisable gift
economies today
are knowledgebased and
conducted over
the internet.

Imagining how a gift economy works can be tricky.
Thinking back a few thousand years to huntergatherer communities where gift economies were
prevalent is helpful. When a hunter makes a kill,
he feels obliged to share his meat in support of his
community and he does so with no expectation of
receiving anything in return. If the hunter fails to
make a kill in the future he will not go hungry as a
fellow hunter will feel the same moral obligations
and share his winnings, thus balancing the situation.
It is difficult to insert this alternative to trade into
today’s capitalist world. However, there are actually
many instances in which members of a community
share their time, skills and belongings as gifts rather

than for trade. Consider the gifting of support
and advice in a group of friends, the gifting of
information and knowledge to others via Wikipedia
and the gifting of programming skills to create free
and open source software for others to use. The
prestige, interest and respect that arise from the
free sharing of a person’s effort can be viewed as the
currency of a gift economy.
But how does gift economics link to science?
The world’s academic scientific research is one
big gift economy. The principle of research lies
in the open exchange of ideas by publication and
the value of this gift to the researcher is that of
a self-organising collaboration. By sharing their
results, others are inspired to ‘return the favour’ by
completing their own research and giving the data
away. This cycle is one of the key driving forces
behind the emergence of exciting new fields in
science. Importantly, a person never has to pay to
stand on the shoulders of giants. The support is given
freely.
This situation is particularly fascinating, as giving
away (publishing) scientific research has genuine
monetary value. For example, many next-generation
sequencing facilities offer two ways to use their
sequencing services. A researcher can either pay a
commercial fee, or enter a formal collaboration and
give the sequencing facility part-ownership of the
intellectual content of the research. A sequencing
facility may give £20,000 in running costs, reagents
and working hours to be included on a research
paper, and then give this intellectual content away
for free in an article. The opportunity to give the gift
of this scientific data is literally worth £20,000. To
understand this counterintuitive situation of giving
something worth money away, you need to imagine
the real currency of a gift economy. While giving
away your ideas and results may seem altruistic, an
individual is actually likely to profit from increased
prestige and interest in their field in the long run.
The uneasy interface between capitalist investment
and academic research
Unfortunately, the features which make a gift
economy work for scientific research are also the
features which make scientific research a difficult
investment for a capitalist economy, especially as

16 | Oxford University Biochemical Society

research is an inherently risky investment. From
a capitalist point of view, there is no value in
giving away research results. In fact, patents exist
specifically to protect intellectual property from
being given away without some kind of trade, the
precise opposite of the gift economy. Capitalism also
views the value of scientific research to others as a
reason to protect and hide it, via patents and trade
secrets, in order to ensure that it retains value in a
trade. Freely sharing this intellectual property is
rarely considered.
This fundamental conflict of interest is one of the
underlying difficulties in interactions between
academic and commercial research. A classic
complaint from commercial pharmaceutical
companies is the lack of patent protection on drug
candidates discovered in universities. From the
researcher’s point of view, it is advantageous to
share their results to promote research in the field.
However, from the drug company’s point of view,
it is vital to obtain patent protection as quickly
as possible to ensure it retains commercial value.
Neither the capitalist nor gift economy can be
viewed as more ‘right’. In isolation both approaches
are perfectly effective, but for a usable drug to be
generated in the long term, researchers must usually
acquiesce to the commercial nature of the drug
industry.
Like any economy, gift economies can break
down. The example of a hunter-gatherer society
illustrates the instabilities of a gift economy well. If
resources become scarce, selfishness will become a
key motivation. During times of drought hunting
becomes difficult. If a hunter is lucky enough to
make a kill, he will be less inclined to share, to
prevent his own starvation. He would only give
away meat in return for something and would only
consider a trade. This situation can easily occur in the
scientific research gift economy. If research becomes
difficult, for example due to a lack of resources, the
motivation shifts away from free sharing. Hoarding
the data, either by protecting it with patents or by
accumulating it for high impact publications to
secure future funding, becomes preferable. This
is arguably why the ‘publish or perish’ attitude,
quantifying research output by number and impact
of papers in order to use it in a trade for further
funding, has become common.
So do we need a scientific gift economy bail-out?
Academic scientific research has undoubtedly
suffered from the recent turmoil in the capitalist
economy. The banks have had bail-outs; does the
scientific gift economy need a bail-out too? It makes
sense to support gift economies when the capitalist
economy is weak, since there is no sense in building
a patent portfolio when there is no money available
to invest in the inventions. It could be far more
advantageous to publish those discoveries quickly to

promote further research in that area. But what form
would a bail-out in a gift economy take?
The health of a gift economy is measured in a similar
way to a capitalist economy. If more gifts are being
given, analogous to increased productivity, the
economy is healthier. By this logic, should we be
promoting pre-publication services, like arXiv.org
for physics research, which allow open peer access
and review prior to publication? And should shorter
times between discovery and publication, or more
presentation of ongoing research in conferences, be
promoted? Is it time to promote sharing of reagents
and methods?
Gift economies may seem unusual but it is important
to support them. Imagine a world where Einstein
did not give away his theory of general relativity for
free but instead stayed working ‘9 ‘til 5’ in a patent
office for cash... But don’t cut up your credit card just
yet. The capitalist model of patent protected research
is also extremely effective as shown by the ongoing
revolution in high-throughput DNA sequencing.
References:
1. Barnes B & Edge D (1982) Science in context:
readings in the sociology of science. MIT Press.
2. Kovac J (2007) Moral rules, moral ideas, and
use-inspired research. Science and Engineering Ethics
13(2):159–169.
3. Mauss M (2002) The gift: the form and reason for
exchange in archaic societies. Routledge.
4. Raymond E (2001) The cathedral and the bazaar:
musings on Linux and Open Source by an accidental
revolution. O’Reilly Media, Inc.

Richard Wheeler is a 4th year DPhil student in the Gluenz and Gull
laboratories,The Sir William Dunn School of Pathology, University of
Oxford.

Hilary 2012 | Phenotype | 17

Targeting the problem:

advances towards effective gene therapy

W

by Annabel
Morley

hen treating genetic disorders such as cystic fibrosis and haemophilia, a fundamental
issue is that every cell in the body possesses a copy of the defective DNA responsible
for the disease symptoms. A successful therapy must target the defective gene in all cells, either
to replace it, modify it or insert a functioning gene into the cells’ DNA to compensate for the
expression of the faulty gene. Scientists have responded to this problem by developing a solution:
gene therapy. This is the delivery of a functioning copy of the gene in question to cells via a
vector, usually an inactive virus or a plasmid that carries the gene to target cells, inserting the
functional gene into an unspecified area of the cells’ DNA.

However there are still the dilemmas of how to
guarantee the vector’s success in delivering the gene
to each cell in the body; how to ensure that the gene
is not rejected as a foreign body; and how to make
the treatment a more permanent solution as once
the gene is delivered to a percentage of cells, other
cells which still possess the non-functioning gene are
dividing and so the disease remains.
Since the emergence of gene therapy in the 1990s
as a viable tool for treatment, progress appeared
to stagnate with limited advancement beyond
discovering that a vector can be used to deliver a
specific gene and the proposal of various methods
to distribute this around the body, for example via
aerosol spray for lung centred diseases such as cystic
fibrosis. However, 2011 has seen a flurry of activity
with the publication of numerous papers highlighting
new vectors, methods to increase permanency, and
techniques to improve vector delivery and success
rates.
Vector delivery improvements
For many diseases, such as amyotrophic lateral
sclerosis (ALS), there are no effective therapies
currently available. However, promising progress
is being made. For example, research using RNAi
and antisense oligonucleotides in animal models
has shown suppression of two genes linked to ALS
pathogenesis, SOD1 and Fas (1). So far however,
clinical applicability has not yet been shown and the
effects on SOD1 have only been demonstrated when
injections are administered directly to the central
nervous system (CNS). Many other treatments
currently being developed for ALS suffer from
similar issues relating to delivery to the correct
site. Without direct injection into the CNS these
treatments, whether pharmaceutical inhibitors or
vectors, have limited success in crossing the bloodbrain barrier, while injection directly into the CNS
has shown success in different animal models.

18 | Oxford University Biochemical Society

Several studies have investigated how to increase the
area which is targeted by the CNS injections (2, 3).
Using a ‘convection-enhanced’ delivery technique,
which utilises a pressure gradient that generates a
mass flow of these agents through the interstitial
fluid space, the delivery of therapeutic agents across a
wider area can be achieved. This propulsion of agents
across a wider space has resulted in the capability to
target a larger area of the brain, showing a promising
advancement for the future. In a recent review,
Salegio and co-workers emphasised the benefits of
using anterograde axonal transport as a transport
mechanism for vectors (4). This is the movement of
molecules from a cell body to the synaptic junction,
moving larger cargo objects such as microtubules
or proteins to a target area. When associated with
an adeno-associated viral (AAV) vector, genes or
agents applied with this method are detected in high
levels in the thalamus. However, a severe lack of any
expression in the cortex will need to be addressed
before further clinical trials can be conducted.
Gene therapy may also be utilised in other disorders,
where rather than replacing a faulty gene it would be
used to insert a gene to increase or decrease levels of
specific proteins or chemicals. Cederfjäll and others
reviewed the efficacy of utilising gene therapy to
administer a constant supply of DOPA, the precursor
of the neurotransmitter dopamine, to Parkinson’s
sufferers in order to improve motor problems
caused by the disease (5). Once again, though
preclinical studies have presented promising results,
there are still issues to be addressed. For example,
improvements to allow DOPA to be delivered
continuously are needed, especially using the current
AAV vector systems.
Vector alternatives
Historically, much gene therapy research has been
aimed at treating cystic fibrosis, where a thick mucus
layer in affected areas inhibits access to target cells.

Viruses such as the human papilloma virus and
the Norwalk virus were used as delivery vectors.
However, a recent study investigating the success
rate of a number of vectors utilised in gene therapy
discovered that most AAV vectors are below average
in accessing target cells when confronted with
human mucus secretions. This may be a reason why
treatments for cystic fibrosis, specifically aimed
at the lungs, have not been hugely successful,
and highlights the importance of selecting the
appropriate vector (6).

EQUINOX GRAPHICS

This data provoked research into non-viral vectors
that could more effectively reach their target cells,
and deliver the gene more permanently and safely
than the viral options currently available. One
such non-viral vector option is the use of chitosanDNA-FAP-B nanoparticles, which exploit the
ability of the fibronectin attachment protein of
Myobacterium bovis (FAP-B) to target epithelial cells,
for delivery to the lungs (7). After nebulising the
nanoparticles, Mohammadi and others administered
the particles to the lungs via an aerosol spray and
discovered that this increased gene expression 16fold compared with chitosan-DNA-nanoparticles.
This type of vector is appealing as the particles are
nonpathogenic. Therefore, the problems linked to the
use of viral vectors, including the potential reversion
“... most adenoto pathogenic states or rejection by the immune
associated viral
system, are avoided. In addition, the use of an aerosol
vectors are below
provides a non-invasive technique unlike direct
average in accessing
injections, as used in previously discussed research.
2. Bobo R, et al. (1994) Convection-enhanced delivery
target cells...”
of macromolecules in the brain. PNAS 91(6):2076–
Looking forward to gene therapy
2080.
It is safe to say that the current increase in clinical
3. Hadaczek P, et al. (2006) The “perivascular pump”
trial successes and the increased ability to target
driven by arterial pulsation is a powerful mechanism
specific diseases indicate that gene therapy may well
for the distribution of therapeutic molecules within
become a valid clinical strategy in the future. Though the brain. Mol Ther 14(1):69–78.
there is a greater body of evidence documenting the
4. Salegio EA, et al. (2011) Guided delivery of adenouse and reliability of viral delivery vectors, there has
associated viral vectors into the primate brain. Adv
been an emergence of several promising non-viral
Drug Deliv Rev doi:10.1016/j.addr.2011.10.005.
options. There has also been increasing research into 5. Cederfjäll E, et al. (2011) Key factors determining
effective options for accurately targeting the affected the efficacy of gene therapy for continuous DOPA
areas of specific diseases. However, there are risks
delivery in the Parkinsonian brain. Neurobiol Dis
associated with invasive techniques such as direct
doi:10.1016/j.nbd.2011.10.017.
injection of the vectors into the CNS and as such
6. Hida K, et al. (2011) Common gene therapy viral
further research is required before they can be fully
vectors do not efficiently penetrate sputum from
accepted as a viable method for patient treatment.
cystic fibrosis patients. PLoS One 6(5):e19919.
In conclusion, gene therapy research has rapidly
7. Mohammadi Z, et al. (2011) In vivo transfection
increased to a point where it is entirely possible
study of chitosan-DNA-FAP-B nanoparticle as a new
that sufferers of many genetic diseases may have
non viral vector for gene delivery to the lung. Int J
an effective treatment in the near future and the
Pharm 421(1):183–188.
possibility of curing such diseases via gene therapy
may be a very distant but potential goal.
References:
1. Nizzardo M, et al. (2011) Research advances
in gene therapy approaches for the treatment of
Amyotrophic Lateral Sclerosis. Cell Mol Life Sci doi:
10.1007/s00018-011-0881-5.

Annabel Morley is a Research Assistant in Prof Charles Godfray´s
laboratory, Department of Zoology, University of Oxford.

Hilary 2012 | Phenotype | 19

Is biotech a fad?
T

by Sonya
Hanson

he reasons for our interest in science can be broken down into two main categories:
we want to know how things work and we hope that our discoveries will prove useful.
The expectation of life science’s ability to be useful has surged remarkably in the last two
decades. With the investment of billions of pounds by governments and venture capitalists in
biotechnology often correlating to media-driven hype, it is sometimes difficult to see the logic
behind the excitement. While it is easy to see the essential role biotech plays in bringing science
‘from bench to bedside’, the relatively few successes among a sea of failures beg a closer look
into the sustainability of ‘biotech’.

In the beginning…
The birth of biotech could be marked by the brewing
of beer or, more recently, milk pasteurisation. Dr
Tamas Bartfai suggests that technically biotech was
born in 1922 when the injection of insulin, crudely
purified from foetal calf pancreas, successfully treated
a dying diabetic 14-year-old boy in Toronto. But
biotech as we know it today began in the 1970s, when
Stanley Cohen and Herbert Boyer first produced
and purified human insulin from bacteria using
recombinant DNA technology. From that Bay Area
discovery sprung Genentech, the leviathan that
anchored the world’s biotech capital. Still, by 1988,
only four more proteins from genetically engineered
cells had been approved by the United States Federal
Drug Administration (FDA) (1).
Wait, how much?
However, the ball had been set rolling and by the
end of the 1990s over 125 proteins from genetically
engineered organisms had been approved. Among
these was alpha-interferon, commercialised by Biogen
for the treatment of multiple sclerosis. Another
development was the production of humanised
monoclonal antibodies by Sir Greg Winter. While
antibodies had been used to treat syphilis since 1910,
broadening the same idea towards effective treatment
of diseases such as hepatitis B and C, auto-immune
disorders and cancer has been invaluable to the
medical community and has been recognised by
multiple Nobel Prizes.

$6.4 to $12.6 billion over the 30 years it [would] take
to pay off the state bonds used to fund it” (2). A later
analysis showed that this was a gross over-estimation
of the benefits, especially given that the study did not
take into account that advances in medicine tend not
to lower the cost of health care, but often raise it as
treatments are piled on top of each other (2).
While we remain decades from knowing if the
investment in stem cell research will pay off, other
examples of government support have fallen flat.
In the late 1980s and early 1990s when companies
like Genentech and Biogen were hitting it big, a
phenomenon of ‘biotech clusters’ arose in which
these companies thrived off the rapid local exchange
of ideas and technology. This phenomenon was
misguidedly embraced by many local governments
hoping to improve their economy by building biotech
clusters of their own, with little more than fancy
buildings and tax incentives. Unfortunately, places like
the Texas Research Park, which broke ground in San
Antonio in 1987 with dreams of attracting 30,000
jobs yet 15 years later had only sustained 300, were
by no means an exception. The strategy did work for
a lucky few, such as Florida’s funding of $510 million
towards a biomedical research facility in Palm Beach
County built by the Scripps Research Institute (3).

While one cannot deny the benefits of combining
good science and good business to make a successful
biotech company, nothing happens in a vacuum. The
early successes of biotech – sheep cloning, mapping
the human genome, stem cell therapy and now
personalised medicine – generated a media frenzy. It
is easy to forget that these successes were by no means
certain and took years of investment to show results,
while many other avenues funded at the same level
and for the same duration failed.

Despite the potential risks and long-term nature
of these investments, and a slew of articles every
few years predicting the ‘pop of the biotech bubble’,
biotech has remained afloat, buoyed in part by the
regular appearance of new and exciting innovations to
entice investors. However, with the recent economic
downturn, and what must now be an increasingly
aware set of investors and governments regarding
the likelihood of immediate returns, biotech startups may now need to look beyond venture capital
and one-off federal investments. Nowadays, even
the viability of the venture capital fund of the man
heralded as starting UK biotech, Sir Christopher
Evans, is in question (4).

In the mid-2000s, New York invested $1 billion in
stem cell research. This was based primarily on a 2004
study that predicted that “stem-cell research would
generate state revenues and health-care savings of

or not’ to a more targeted approach, with distinct
strategies toward certain emerging markets. This
trend coincides with venture capital’s changing focus
towards biotech companies in their later, safer stages
of development. It is hoped that venture capital
investment in early stage biotech will recover with
the economy, but this seems unlikely unless certain
standards are set in place to help stabilise start-ups.
This known risk is an important reason why start-ups
tend to follow trends, which appear safer, but this is
not the ideal climate for the development of the drugs
that are really needed.
Dr Tamas Bartfai spoke to OBR about this gap
between science and drugs. Pharma and biotech
focus disproportionately on targeting diseases such
as diabetes and cancer, simply because the science in
these areas is already well established, clinical trials
are quick and thus risks are low and profit more likely.
Antipsychotic drugs and new antibiotics to combat an
impending ‘superbug’ are ignored as they are riskier
and more expensive to develop.
This is a gap that a commercial approach to medical
science is not prepared to fight head-on and that must
be tackled with the help of government health funds
and academic scientists. With Dr Francis Collins’
creation of the National Center for Advancing
Translational Sciences at the NIH in Bethesda,
MD, and the Royal Society of Chemistry’s recent
funding from Parliament to be directed toward drug
discovery, there is an obvious push towards reducing
our dependence on biotech start-ups to get the drug
discovery pipeline moving. Government funding
for biotech and biological sciences has been around
for a long time, but the recent push to eliminate the
hyper-competitiveness of early biotech via formal
programmes is new. Some biotechs now engage in
‘pre-competitive alliances’, where companies exchange
ideas and technology in a series of agreements.
However, these alliances come with heavy regulations
and many caveats. Another excellent example of
this type of collaboration is the increasing number
of graduate programmes, such as that funded by
the BBSRC, which allow students to have both an
industrial and an academic mentor.
With the low-hanging fruits of early biotech now
fully developed, and a market that is gradually less
impressed by each shiny new breakthrough, perhaps it
really is time for biotech to settle into its proper niche
between academic and commercial medicine. This
theme was even picked up at the Structural Genome
Consortium, which is holding a conference in January
2012 titled: ‘Drug Discovery: A job too complex for
academic or industry alone’.
References:
1. Colwell RR (2002) Fulfilling the promise of
biotechnology. Biotechnol Adv 20(3-4):215–228.

Dr Tamas
Bartfai spoke
to OBR about
risk-avoidance
by pharma and
biotech leading
to a bias in the
kinds of diseases
targeted.

Oxbridge-London Biotechnology Roundtable
(OBR: http://oxbridgebiotech.com) is an intercampus forum connecting industry professionals
to academic innovators with a mission to foster
an on-campus conversation about biotech,
pharmaceutical and the life sciences industry.
An expanded version of this article appears on the
Roundtable Review (http://www.oxbridgebiotech.
com/blog), the online publication arm of OBR.
Get in touch with us at blog@oxbridgebiotech.
com if you’d like to contribute your own voice to
the conversation.

Sonya Hanson is a 3rd year NIH-Oxford DPhil student in the
Department of Biochemistry. She is supervised by Dr Simon Newstead
and Prof Mark Sansom at Oxford and Dr Kenton Swartz at the NIH.

Hilary 2012 | Phenotype | 21

European approaches to GM:
Understanding the policy dilemma in a global context
By Mark
Pavlyukovskyy

O

n 31 October 2011, the seven billionth person on the planet was born in Manila, the
Philippines. Both the Russian and Indian governments claimed that babies born in their
countries also held this symbolic status, yet this happy occasion highlighted one of the most pressing
challenges facing today’s world. With the world’s population projected to reach nine billion by 2050,
what rate of population growth is sustainable?

Impetus for GM development
The consequences of overpopulation are devastating.
Resources become scarce and the carrying
capacity of the planet is exceeded. Poor farming
practices, topsoil erosion and a lack of water lead
to desertification, which in turn decreases the
proportion of arable land and is indirectly responsible
for close to one billion people across the globe
going hungry every day. In developing countries,
a staggering 30,000 people, the equivalent of the
student population of Oxford University, die of
hunger every day. Technological advances, including
the use of agrochemicals, fertilisers, mechanisation
and improved quality of seeds, have helped to double
food production over the past several decades, even
though arable land has only increased by 10% during
that period. However, most of these techniques have
negative impacts on the environment, including
algal-induced anoxic dead-zones in bodies of water
where phosphates and nitrates have run off, as well
as the siphoning-off of large quantities of water to
irrigate fields, and the harmful effects of pesticides
on biodiversity.

covered up uncertainties in the evidence while expert
advice had downplayed potential risks (1).
Following these troubles, there was an attempt
by the European Union (EU) to enhance expert
credibility and establish a risk-assessment process
that was separate from the risk-management
process. To this end, new legislative bodies were
established, including the European Food and Safety
Authority (EFSA), allowing for a more rigorous and
transparent evaluation of food safety. It is useful to
note that this decision to create a new system to cope
with the problems in food safety, including GM
crops, was in stark contrast to the decision in the
United States to utilise the already-present system
in the form of the Food and Drug Administration,
as well as the Environmental Protection Agency, to
oversee the GM crops approval process.

Improved plant breeding strategies, including genetic
modification (GM), have been seen as a progressive
technological solution with very few negative effects.
In the United States, upwards of 85% of cotton, corn
and soybean crops are genetically modified. The
engineered resistance to herbicides or insecticides
allows for higher yield and better quality crops, with
decreased use of expensive, non-specific insecticides,
making GM agriculture also an economically
superior solution.

GM crops in Europe: introduction and ban
GM crops were introduced and championed
in Europe by large agricultural biotechnology
companies. The largest and best-known of these
are the American company Monsanto and, to a
lesser degree, the Swiss company Syngenta. With
the food crises of the 1990s in mind, European
consumers were very sceptical of large companies
altering food crops for the sole purpose of making a
profit. Non-governmental organisations (NGOs) like
Greenpeace amplified these fears by staging mass
media campaigns to alert people to the ‘untested’
and ‘untried’ aspects of GM crops. Moreover, GM
crops were easy to vilify due to the type of genetic
modifications that are made.

European food safety regulation
While GM crops have been widely adopted
across the Americas and parts of Asia, they are
conspicuously missing from Europe. The reasons
for this can be traced to Europe’s history with food
regulation, which has been notoriously unstable. In
Europe, food safety and authorisation have resided
primarily in the realm of specialised scientific
bodies, which would then give the impetus for policy
decisions. Yet as the ‘mad-cow disease’ and dioxin
crises in the late 1990s demonstrated, this system
was not ideal, since the European Commission had

Monsanto, and indeed almost all companies
involved in GM crops, produce genetically modified
organisms (GMOs) with ‘input trait technology’.
Such modifications are exclusively limited to
herbicide tolerance or insect resistance. The resulting
benefits are realised mainly by farmers through better
yields and lower cost, and are felt only marginally by
consumers in the form of lower prices. For Monsanto
and other companies, there is a huge incentive to
produce plants with these traits because in their main
market, the United States, growing such crops on an
enormous scale offers large profit margins.

22 | Oxford University Biochemical Society

For American consumers, who had not experienced
food crises on the same scale as in Europe, GM crops
were simply a cheaper alternative at the supermarket.
By contrast, for European consumers, GM crops
were an untested and potentially dangerous
product that offered them little, while allowing
large companies to make large profits. NGOs like
Greenpeace were able to capitalise on this and paint
a picture of GMOs as ‘Frankenstein Food’ that had
as its sole purpose increased revenue for large foreign
companies. These negative attitudes towards GM
crops provided the impetus for EU member states to
use legal loopholes to avoid authorising GM crops for
cultivation in their territories, which created many
problems for the European Commission and resulted
in a case being brought against the EU for the
violation of World Trade Organisation agreements.
The irony of the cultivation bans in EU member
states is that Europe imports 80% of its animal feed
from America and Brazil in the form of soybean and
corn, where over 90% of the exported crops are GM.
Owing to the large cost to farmers of importing
non-GM feed, member states have begun allowing
European farmers to use GM feed. This presents
the European Commission, the body responsible
for authorisation of GM crops, with a dilemma in
that home-grown GM crops are no different from
imported GM crops and the basis for the GM ban in
member states is coming to be seen as very tenuous.
To ban or to...?
There are several policy alternatives that the
European Commission could implement. The most
straightforward option would be to allow member
states to be part of the decision-making process.
This could be achieved by creating a rotating ad hoc
‘Independent Expert Council’ comprising a group of
outstanding research scientists representing all EU
states. The decision-making process would acquire
legitimacy and credibility among member states,
ensure representation and incorporate the latest
knowledge into the decisions. Another option would
be to enter into a dialogue with, and educate, the
public through initiatives where people would receive
objective comparative information about available
agricultural production methods (conventional,
organic and GM), along with their advantages
and drawbacks in terms of human health and
environmental sustainability. People would be offered
crops with ‘output trait technology’, including food
with increased nutritional value, which would be
presented as useful and practical for their needs.
Finally, it would be constructive to create publically
funded ‘Independent GM Research Centres’,
possibly affiliated with a research university, which
would conduct cutting-edge research on the use of
GM organisms to combat disease and improve

human nutrition. This would turn over the control of
genetic modification research to the public from the
for-profit global corporations. Allowing unopposed
scientific investigation, which is presently only
possible as a result of funding from large companies,
would increase the European public’s trust of GM
crops, and encourage more research in this field.

“NGOs like
Greenpeace were
able to capitalise
on this and paint a
picture of GMOs
as `Frankenstein
Food`.”

Mark Pavlyukovskyy is a 3rd year undergraduate student from Princeton
University, working in Prof Jonathan Hodgkin´s lab, Department of
Biochemistry, as part of the Princeton/Oxford exchange.

Hilary 2012 | Phenotype | 23

BOOK REVIEWS
Fungi – Biology and Applications (Second Edition).
Edited by Kevin Kavanagh
ISBN: 978-0-470-97709-5,Wiley-Blackwell (October 2011), Paperback, 376 pages, £34.95
Reviewed by Jennifer de Beyer
Fungi – Biology and Applications is billed as an introduction to all aspects of the fungal world and research,
suitable for an undergraduate or newcomer to the field. It covers the diversity of fungal metabolism,
physiology and growth, and focuses on how this diversity impacts and is utilised by man through
fermentation, therapeutic and biotechnology applications.
The text deals particularly well with genetic analysis of fungi and fungal proteomics. Both the molecular
biology and protein biochemistry required to generate data and the ‘omics’ analysis tools are covered.
Assuming very little prior knowledge, these techniques are explained in the context of specific advances in
understanding of fungal physiology, providing a good link between theory and research.
Chapters dealing with the economically and medically important aspects of fungi are packed full of facts, yet
maintain an easy pace. The authors show good knowledge of both their subject field and their audience, with
fascinating discussions exploring exactly how one produces a pint of the perfect hue and the alcohol content
of bread dough around the world.
Again bearing in mind the intended reader, each chapter closes with a short recommended reading list rather
than a lengthy reference section and a useful set of review questions, the answers to which are provided in an
appendix.
However, a lack of care in production means quality varies significantly between chapters. In most chapters,
the layout is clear and the writing style easy to follow and engrossing. In others, convoluted sentence
structure and heavy writing leaves the reader confused and bored. Worse, in-text references to images are
incorrect. In some cases, captions are incomprehensible due to lack of a key and in others are quite simply
wrong.
It is a great shame, as the breadth of information contained in Fungi – Biology and Applications and
its generally engaging tone should make it well suited as an introductory text. However, the errors are
sufficiently numerous and distracting that I would not recommend this book in its current edition.

The Magic of Reality: How we know what’s really true
Richard Dawkins
ISBN-13: 978-0593066126, Bantam Press (15 September 2011), Hardcover, 272 pages, £8.00
Reviewed by William Brandler
While growing up I had heard of dinosaurs, DNA and Darwin, but I had no real idea about the evidence
for evolution. I believed in it because it was presented to me as a fact in school. In The Magic of Reality,
Richard Dawkins shows how science can answer the big questions in which children may be interested, such
as: “Why do bad things happen?” and “Who was the first man?” Although it is pitched at 12 year-olds, the
broad nature of the topics covered and his elegant style of prose make this book appealing to adults as well.
First Dawkins details other attempts to answer these questions. Children may be aware of Adam and Eve,
but not of the countless other creation stories in different cultures. What is clear, although he is not explicit
in saying so, is that not all of these myths can be true. He then explains the evidence for evolution, which is
so compelling and wonderful in comparison, that it makes myths seem absurd.
As Dawkins explains, myths don’t tell us “how old the universe is; they don’t tell us how to treat cancer; they
don’t explain gravity or the internal combustion engine; they don’t tell us about germs, or nuclear fusion, or
electricity, or anesthetics”. He doesn’t skirt around difficult concepts, using complicated words like perihelion
and metastasis, explaining them in a clear and unpatronising way.
For a child growing up in a community where myths, the supernatural and magic are presented as reality, a
book like this can be empowering and I would highly recommend it.

24 | Oxford University Biochemical Society

SCIENCE and SOCIETY
Volunteering at Science Oxford
Have you ever cycled towards Headington and wondered what is in the glass building marked with
a purple sign just below the hill? Well, this is Science Oxford, our local science centre which aims
to make science more accessible through providing education and engagement activities for the
general public. As someone who has been volunteering there for the past couple of years, I wanted
to introduce the centre to University of Oxford students and staff who may also enjoy getting
involved.
One of the most well attended events hosted by the
centre is the Thursday evening talk. It sometimes
feels like Oxford is saturated with scientific
presentations, but the twist with those at Science
Oxford is that they are aimed at people without
a science background. So anyone can listen to a
talk about quantum physics without feeling lost!
Volunteers are involved in these regular talks,
helping ‘front of house’ prior to the session. This
involves mastering the ever-so-complicated till,
ushering people to the lecture room, webcasting and
recording the talk. Volunteers can also listen to the
talks, so you can sign up to help at the events you
want to attend.
As well as helping at talks, you can volunteer in
other ways. Firstly, you can write for the Science
Oxford Online blog. This is a depository for sciencerelated articles aimed at the general public and
includes reviews of the Science Oxford Live talks.
As a volunteer at the event, you are well placed
to review the talk afterwards for Science Oxford
Online. The blog may also be of interest to budding
science writers as any articles are welcome, providing
they are scientific in nature and suitable for general
consumption. So do think about writing for the blog,
even if you do not have time to volunteer at the talks.
Although time-consuming, the most satisfying way
of getting involved is to present a talk yourself. I
have done this and it seemed more challenging than
presenting to peers in a departmental seminar or at
a conference. You certainly have to be mindful of
the diverse levels of knowledge within the audience
– you could be talking to anyone from a retired or
active Oxonian professor, through to someone whose
science education ended at the age of 14. With this in
mind, I chose not to talk about the intricacies of my
research, but rather ‘science behind the headlines’.
For this, I compared the reporting of science articles
by different news outlets ranging from BBC News to
The Sun. Using the original journal article abstracts,
I discussed a number of points to look for in order to
assess the credibility of the reporting. To elaborate,
I discussed the concept of a fair scientific trial,
introducing aspects of control and randomisation
with Smarties ‘tablets’, concepts which seemed to be
well received by the audience.

Finally, the centre hosts a Discovery Zone which
Dr Blanka
contains science-based, hands-on exhibits open to
Sengerová
primary school students during the week and the
general public on weekends. Using the Discovery
Zone and adjacent activity space, the staff at Science
Postdoctoral
Oxford also run holiday Science Clubs, and have
researcher in the
recently initiated a Saturday Science Club for
DNA Damage and
children (some aimed at five to seven year-olds and
Repair lab at the
others at eight to eleven year-olds). This is another
Weatherall Institute
great opportunity for volunteers to get involved.
of Molecular
Medicine.
If you are interested in volunteering at the Thursday
talks and want to find out when the next training
session will take place, you can contact the volunteer
co-ordinator, Emma Clare. Alternatively, if you
would prefer to get involved on the writing side, the
Science Oxford Online blog is run by Carl Anglim.

As Forever Young playing on my next door neighbour’s
radio echoes in the background, I realise that I am
two hours away from the Phenotype article submission
deadline. I open a new tab in Firefox: “define:
procrastination”. Hello. My name is Andrea and I am
a procrastinator.

1st year DPhil
student on the
Doctoral Training
Centre Systems
Introducing ‘Piled Higher and Deeper’ (PhD) Comics
Biology programme PhD Comics is probably the finest example of a
procrastination source for graduate students. It
brings together grads from all over the world as they
commiserate over the pains and sorrows of being
a graduate student. If you have no idea what I am
talking about, then you are probably not a graduate
student.

The comics themselves started off as a means of
procrastination for Jorge Cham, then a PhD student
in Mechanical Engineering at the University of
Stanford, USA. The first comic was published on 27
October 1997 with a new comic appearing on average
2.7 times per week. After completing his PhD, Jorge
spent a few years as a researcher at Caltech. He is now
dedicated full time to PhD Comics and lately, PhD
The Movie.
‘Piled Higher and Deeper’ The Movie
Now, some 14 years after the first comic, Jorge
has produced a film based on the comics. It was
filmed at Caltech without the help of professional
actors or producers. The whole project was carried
out by graduate students and researchers, with
contributions from other staff members at the
university.
The film aims to provide a more realistic view of
the unique and, let’s face it, often funny world
of academia. As Jorge points out, there are not
enough stories about scientists in popular culture
and the existing ones place far too much emphasis
on eccentricity and the ‘mad scientist’ stereotype.
The film follows the characters from the comic
(Cecilia, Mike, Tajel and the ‘Nameless Grad
Student‘) in their attempts to find a balance
between research, teaching and their personal
lives.
Auditions were organised at Caltech and
standards were high; Alexandra Lockwood
who plays Cecilia confesses she has had a long
history of involvement with performing arts,
ranging from being part of a play in high school,
to having sung a (rather bad) song in a musical.

26 | Oxford University Biochemical Society

Many people have wondered who the person playing
Professor Smith is. He is indeed part of the world
of academia, but he is no academic. He is one of
the IT officers at Caltech – that’s right, he fixes the
computers of Nobel Prize winners. Interestingly
enough, the ‘Nameless Grad Student’ was in fact
played by a first year undergraduate. This seems to
have helped a lot in terms of conveying genuine
surprise when faced with certain aspects of graduate
life. Perhaps the bad news is that he now wants to
become a graduate student.
One might wonder how those graduate students in
Caltech managed to find the time to get involved in
such a project. Alex explains that her supervisor was
quite supportive when she told him, last minute of
course, that she was going to be in a film: “Weekends
and long hours, that’s how I managed it”. Jorge adds
that Alex’s tiredness ended up being advantageous for
particular scenes in the film.
Another unique aspect of PhD The Movie is that it
is not screened in cinemas but rather on university

SCIENCE and SOCIETY
campuses across the world. It is a film made by
graduate students and researchers for graduate
students and researchers. The Oxford University
screening, held in the Examination School, was
made possible by the contributions and efforts of the
Oxford University Student Union (OUSU) and the
Mathematical, Physical and Life Sciences Division,
along with a team of enthusiastic graduate students.
For those of you who could not get a ticket for the
first screening (to be fair, the tickets did sell out in
eight hours), all is not lost! A second screening is
going to be organised, most likely in Hilary term
2012. People have asked if the film is worth seeing. If
you like the comic, then it definitely is!
Jorge Cham in Oxford
Thus, PhD The Movie came to Oxford. Thanks to
a generous contribution from The Times Higher
Education, we were able to have Jorge Cham and Alex
Lockwood attend and hold a Q&A session after the
film. A few of us were lucky enough to spend half a
day as their guides. It was a refreshing experience, as
if we were showing a couple of old friends around
Oxford. After meeting them at the train station, our
first destination – before even such Oxford landmarks
as Christ Church College – was G&D’s ice cream
cafe. Jorge and Alex were impressed and at times
amused with the ’Disney world of Academia’ that was
unravelling in front of them as the tour progressed.
Many people have asked what Jorge Cham was like.
“Jet-lagged”, would be my answer. And one would
expect nothing less, given that he is zigzagging across
time zones to introduce the film. Appearance-wise,
you can tell where the inspiration for the ‘Nameless
Grad Student’ in the comics came from; the hairstyle

is unmistakable. Jorge is a relatively quiet person,
although this might have been the jet-lag, and you can
most definitely see the distinct humour of a person
who has gone through grad school in him.
Back to the lab...
Procrastination is a serious issue. However, it is
arguable that a controlled dose of procrastination
helps keep us graduate students sane. When
experiments don’t work, when equipment fails, when
you haven’t seen actual sunlight for days, you need
something to lift you up. This input may not come
from your lab mentor, who is probably trying to make
the deadline for a paper, your colleague, who needs to
stand by his reaction day and night, or your supervisor,
who is too busy anyway. It is at this point you begin
to venture into ‘the hollow world of the interwebs’ to
seek comfort.
PhD Comics do a great job in this respect. Many of
the comics are inspired from stories e-mailed to Jorge
by the readers. “They e-mail me stories and I draw
up the comic”, Jorge explains. This way, the comics
have become a global project, with contributions from
graduates everywhere. The comics give you that pat on
the back; they tell you that even though you are the
only person in a windowless room, you are not alone.
And this gives you the strength to carry on, make
the experiment work and write a grant proposal to
purchase new equipment, to go out there, show your
work to the world and submit the thesis!
References:
www.phdcomics.com

Write for Phenotype?
• The deadline for article submissions is Friday of 8th week, 9 March 2012
• We accept articles on any aspect of biological sciences research, books or science
education
• Articles can be either 650 or 1300 words
If interested, please get in touch: oubs@bioch.ox.ac.uk.

Work for Phenotype?
If you’d like to get involved in editing, production or management of
Phenotype, please get in touch: oubs@bioch.ox.ac.uk.

The Athena SWAN Charter scheme was developed in 2005 to recognise excellence in Science,
Engineering and Technology (SET) for women employed in higher education. Its goal is to improve
the representation of women in science by placing an effective framework within the workplace for
diagnosing gender gaps, drawing up action plans and committing to progress on gender inequality.

2nd year DPhil
student in the
Department of
Anatomy, Physiology
and Genetics.
Graduate Women’s
Officer for the
Oxford University
Student Union.

Our Medical Sciences Division will face a loss
of £100 million in National Institute for Health
Research (NIHR) funding by 2015 if it fails to
show it is taking sufficient and effective action on
gender equality by achieving Athena SWAN Award
silver status. In a public letter on 29 July 2011, the
Chief Medical Officer of the Department of Health,
Professor Dame Sally Davies, issued an ultimatum
to all medical schools in the UK in which she stated
that she was “appalled on behalf of our nation” by the
lack of thought that medical schools had put into
improving gender equality in science.
Award principles
Currently, there are 68 members (approximately
51% of eligible higher education institutions) of the
Athena SWAN Charter, each awarded either bronze,
silver or gold status upon application. The awards
recognise the good practice of its members on the
recruitment, retention and promotion of women
in SET in higher education and research, striving
to increase the numbers of women recruited to top
posts within SET roles. Awards are made on how
well departments and universities incorporate the six
Charter principles into their action plans: addressing
gender inequalities; changing cultures and attitudes
across the organisation; examining the implications
of gender homogeneity at management and policymaking levels; tackling the high loss rate of women
in SET; recognising that the current system of
short-term contracts has negative consequences for
the retention and progression of women in SET;
and actively considering the personal and structural
obstacles to women making the transition from a
PhD into a sustainable academic career.
The University of Oxford and Athena SWAN
Oxford University as a whole holds a bronze award,
renewed in 2010, showing its commitment to creating
gender equality within its departments. However,
only the Zoology department holds a silver award.
The university is encouraging its SET departments to
apply, as it will only move forward to silver and gold
level if it shows a significant record of activity and
achievement across the full range of SET disciplines,
with a substantial number of departments holding
individual awards.

28 | Oxford University Biochemical Society

Sarah Hawkes, senior policy adviser at the Equality
Challenge Unit, who is responsible for the Athena
SWAN award, commented on the achievements:
“We are pleased that these successes are encouraging
other departments within Oxford to embark on
the Athena SWAN process, and we hope that good
practice continues to be shared within and outside the
institution”.
Getting involved with Athena SWAN
The key to a successful Athena SWAN application
is the support and energy of the department in
conducting its Athena SWAN self-assessment, and
in delivering on its action-plan. Only by having an
overarching view of the problems in maintaining
gender equality and diverse ideas on how to address
these problems at each step of the academic ladder,
from undergraduate level to tenured academics and
technical staff, will the gender imbalance be addressed.
Everyone is encouraged to get on board. You can
get in touch with your Head of Department and
volunteer to be a representative on the Committee.
You can also hold evidence-gathering consultations or
surveys or simply participate in them.
Getting involved, in whatever way, means a lot. The
award is presented to departments who show they are
taking constructive initiatives to make progress on
equality, not merely achieving gender parity in staff
or student figures. Furthermore, although the Athena
SWAN Award is aimed at gender equality policies
and initiatives, the best equality-promoting initiatives
ultimately improve the experience and atmosphere for
everyone in the department.

5´ with... Professor Adrian Hill
I was hooked. It was a very exciting time for science
– the techniques that were just coming through like
PCR were amazing. You realised that everything
science had been waiting to do for years, for example
sequencing bacterial genomes, we were now going to
be able to do. I did two more clinical years and then
went back to research.
If you were not a scientist, you would be…
When I was seven, plan A was to be an astronaut!
But to be honest, I would probably be a medic.
If you are not in the lab you are…
On an aeroplane. Most scientists have two reasons
to travel, firstly to go to conferences to present work
and secondly to network and build collaborations.
But when you work on tropical medicine you have
another – you have to travel to get to where the
action is.

A

drian Hill was appointed director
of the Jenner Institute in 2005,

after co-founding the Oxford Centre for
Clinical Vaccinology and Tropical Medicine.
His group focuses on the development of
prime-boost malaria vaccines.
Interviewed by Amy Baxter
When did you first decide you wanted to be a
scientist?
When I was a houseman, I got an MRC training
fellowship to work towards a DPhil with Sir David
Weatherall. I met with him, expressed my interest in
the work that was going on in the lab and asked if I
could join his group. He mentioned some collections
from Vanuatu that could be of interest and I just
said yes. I committed myself without even knowing
where Vanuatu was! The first thing I did was go to the
library to look it up in an atlas and it didn’t exist, it
was only recently renamed and had formally been the
New Hebrides. I completed my DPhil analysing the
population genetics of Pacific Islanders and after that,

What was your worst disaster in the lab?
That’s easy. One day a postdoc from the lab walked
in almost in tears. She had noticed tumours in one
mouse from a vaccine study and hadn’t thought
anything of it, but that day she saw tumours in two
more vaccinated mice. This was a vaccine type that
we were already using in a clinical trial! Obviously,
we had to stop the trial and work out what was
happening. It was a very scary month until we
realised that the mouse strain we were using had a
mutation that made them susceptible to spontaneous
salivary gland tumours and it was nothing to do with
the vaccine.
What has been the most memorable finding of
your career so far?
The most memorable finding was many years ago
when we were looking for the first CD8+ T cell
responses to malaria. I had made malarial peptides
that we had predicted might be recognised by a
certain protective HLA type and took them to Africa
to test. This was in the days when you made your own
peptides, a horrible, smelly procedure that made you
very unpopular in the lab. One morning we drove to
a village clinic, saw HLA-typed patients and did the
assays, testing responses to the peptides that evening.
The first few were negative, but then at midnight a
critical sample was positive. It was from a woman
who had the HLA-type associated with malaria
resistance. She had responses against liver-stage
malaria antigens, just as we had predicted. It all fell
into place.
What is your favourite conference location?
You need two key things for a great conference – you
need the right people and also you need them to be

Hilary 2012 | Phenotype | 29

5´ with... Professor Adrian Hill
locked away without any other distractions, apart
from skiing! Probably the best place for this is Cold
Spring Harbor on Long Island in summer and a
Keystone ski resort in winter.
What is the best advice you have ever received?
Work on an important problem. Peter Medawar
wrote a book published in 1981 called Advice to a
Young Scientist. In it he said, “don’t try to solve piffling
problems, because you will get piffling answers”. That
was rude language for his generation, but he was right!
Do you have a favourite classical experiment?
There was a graduate student at Exeter College called
Anthony Allison who was in the third year of his
DPhil and didn’t really have any data, so decided to
go to Uganda to collect some. While he was there
he discovered that sickle haemoglobin is protective
against malaria – in 1953! It was the only gene he
had looked at. However, although he was right, lots
of people didn’t believe him. In 1964 he wrote a
passionate defence concluding that “I can’t see what
further evidence any reasonable person would want

to have”. It’s the same way we all feel when a reviewer
rejects a paper.
In your opinion, what makes a good scientist?
The really good ones are prepared to ignore the
popular topics, the fashions, and search for something
that has been missed, something that would make a
difference. They keep going even when it’s difficult,
despite what anyone says. Getting a grant rejected
doesn’t stop good scientists; it just delays them.
How do you imagine biological research will
change over the next twenty years?
It will become far more computational, like it already
is in genetics. It used to be the case that you spent
90% of the time in the lab at the bench and the rest
at a computer. Now it’s 90% at a computer and the
rest spent sending off samples for high-throughput
sequencing. I also think there will be more networking
and more ‘big science’. I fear it will be much less about
small projects, which is a shame because good science
often comes from small groups of determined people
with big ideas.

Explore the latest books in Cell and Molecular Biology

All Phenotype readers can save 20%
on books by using promo code
LIFE at the checkout
www.wiley.com/go/lifesciences

Like Cell and Molecular Biology?
There’s a button for that!
facebook.com/cellandmolecularbiology

Digital versions are available online

11 - 3 6 9 2 9

SNAPSHOT

Research Image Competition

This issue´s winner is...
Dr Elizabeth
Hartfield
A career development
fellow in Dr Richard
Wade-Martins’
laboratory in the
Department of
Physiology, Anatomy
and Genetics.
Her image shows a differentiating neurosphere that was
generated from a human induced pluripotent stem cell
line. After 45 days of differentiation, cells were fixed and
stained for the neuronal marker Tuj1 (red) and nuclear
DNA (blue), and images were captured using confocal
microscopy. Large neuronal processes can be seen
migrating outwards from the centre of the sphere while
cell bodies remain within the sphere.
In recognition of her contribution, she will receive a £50
book voucher kindly provided by our sponsor Oxford
University Press.

After completing her PhD in Molecular Neuroscience at Bristol University, Liz joined Dr Wade-Martins’
laboratory in April 2010. Here she is part of a large team of researchers studying neurodegenerative diseases,
including Parkinson’s and Alzheimer’s. Specifically, Liz is utilising the latest cellular reprogramming
technologies to develop models for early stage Parkinson’s disease (PD).
PD is a progressive neurological condition that results in the loss of dopaminergic neurons. The consequent
reduction in dopamine levels leads to the symptoms of PD, which most commonly include tremor, rigidity
and slow movement. There are approximately 120,000 PD patients currently living in the UK, the majority of
whom are over 50. The exact causes of PD remain poorly understood and, although there are drugs available
to help relieve the symptoms of the disease to some degree, there is currently no cure.
Liz’s research uses small skin samples from both PD patients and healthy donors. Viral vectors are used to
deliver five reprogramming factors (OCT4, Sox2, KLF4, nanog and c-myc) to the skin-derived fibroblasts.
These factors reset the differentiated status of the cells to a stem cell-like state, producing induced pluripotent
stem cells (iPSCs). The iPSCs can then be differentiated into dopaminergic neurons, the cells that degenerate
in PD brains. Researchers in Dr Wade-Martins’ group are amongst the first in the world to successfully
differentiate functional dopaminergic neurons from iPSCs, which are in turn derived from PD patients.
“These cells express midbrain dopaminergic markers, are electrically active, and produce the neurotransmitter
dopamine, which is incredible considering that they were once skin cells!” explains Liz.
Many valuable insights into the end stages of PD have been obtained using human post-mortem brain
tissue. However, post-mortem samples are of limited use when investigating the early molecular mechanisms
involved in PD development. The use of reprogrammed cells will allow researchers to obtain human midbrain
dopaminergic neurons derived from PD patients for the very first time, enabling the early stages of PD to be
studied more effectively. “We are essentially developing a ‘disease in a dish’.” The ultimate aim of this research
is to develop improved treatments for this debilitating disease.

Win a £50 book voucher kindly provided by Oxford University Press!

SNAPSHOT

Research Image Compettion

Do you have an image from, or inspired by your research? Why not enter it in SNAPSHOT?
We are now accepting entries for pictures to be featured on the cover of Phenotype TT 2012.
To enter, send images to oubs@bioch.ox.ac.uk with a brief description (maximum 100 words).
Please get permission from your supervisor before sending any images. There is no limit to the
number of entries per person.
The deadline for the competition is 9 March 2012.

PHENOTYPE

crossword
Enter the competition by sending your answers to
oubs@bioch.ox.ac.uk or leave a paper copy in a
sealed envelope in the OUBS pigeonhole at the New
Biochemistry reception. Entries received by 9 April
2012 will be entered into the prize draw.

The winner will receive
their choice of two books
reviewed in this issue,
generously provided by
Wiley-Blackwell.